NSF-BSF: Computational and Experimental Design of Novel Peptide Nanocarriers for Cancer Drugs

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Peptides are short chains of chemically linked amino acids. Peptide-based materials are highly promising carrier agents for cancer drugs, because they offer the potential to improve anti-cancer efficacy while reducing the side effects of the constituent cancer drugs. These materials also feature ease of fabrication, potential biocompatibility, and tunable chemical properties. There are, however, significant challenges associated with the application of peptide-based materials as cancer drug nanocarriers. The goal of this project is to build on promising initial work with a specific peptide (cyclo-dihistidine or cyclo-HH). The researchers will use computational and experimental methods to develop novel classes of “smart” peptide-based nanomaterials for delivery of the cancer drug, epirubicin. This nanocarrier design process will be based on peptide self-assembly mechanisms that permit improved therapeutic properties. The project also involves educational activities to promote interdisciplinary training of undergraduate and graduate students and to add an international dimension to their research experience. The research team also will be involved in outreach efforts to underrepresented high-school students.The research aim of this project is to develop a novel classes of cancer drug delivery nanocarriers. The research team will pursue computational and experimental studies to examine whether cyclo-dihistidine can serve as a “universal” nanocarrier self-(core/shell) encapsulating cancer drugs of different structural and physicochemical properties and how different processing conditions may affect drug self-encapsulation. The researchers also will design peptide nanocarriers combining enhanced fluorescence and high binding affinity to cancer drugs in mixed peptide-drug arrangements. Finally, the team will transform the most promising nanocarriers into smart drug nanocarriers capable of targeting cancer cells through co-assembly with CXCR4-targeting peptides. The resulting peptide-materials are expected to be a viable alternative and promising route to delivering cancer drugs, fruitfully combining ease of fabrication with a range of capabilities including enhanced fluorescence to enable monitoring of drug release, optimized drug encapsulation, and improved targeting of cancer cells. Apart from highly promising new materials, the research project will create a computational protocol offering transformative new means for the design of functional peptide-materials serving as cancer drug nanocarriers.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.